Optical sensing devices that use effects based on the amplitude, phase, frequency, and state of polarization of electromagnetic radiation are known (see e.g. T. Hirschfeld, J. Callis and B Kowalski, “Chemical sensing in process analysis”, Science, vol. 226 (1984) 312-318]. In chemo- and biosensors, all possible interactions between radiation and matter such as dispersion (refractive index), reflection (diffuse and specular), scattering (Raman), changing transmission, or quenching of fluorescence have been applied to monitor analyte/sensor interactions. Devices based on total internal reflection and evanescent-field effects are also known (see e.g. O. S. Wolfbeis, “Analytical chemistry with optical sensors”, Fresenius Z Anal. Chem., vol. 325 (1986) 387-392). The aim of most development efforts in this field is toward achieving label-free, simple and cheap sensors with high sensitivity and specificity.
A sensitive layer comprising either a chemical or a biological (‘receptor’) material (also referred to as a “probe”) is an essential part of chemo- and bio-sensor systems. As the difference between a chemical sensor and a biosensor lies mainly in the nature of this sensitive layer, the sensing principle being the same, we will refer henceforth to “biosensors” only, with the understanding that the present invention applies equally well to chemo-sensors. A good recent review of various types of optical biosensors and sensing principles may be found in U.S. patent application Ser. No. 20040078219 to Kaylor et al.
Label-free biosensors include in particular biosensors based on grating waveguides, some of which are sold commercially (see e.g. the OW 2400 sensor chip manufactured by MicroVacuum Ltd, Budapest, Hungary). These types of sensors couple a laser beam into the waveguide layer, and the in-coupling angle is very sensitive to the presence of absorbed molecules and to any change in the refractive index of the medium covering the chip surface. The amount of material absorbed on the grating can be determined sensitively from a precise measurement of the in-coupling angle (“angle interrogation”). Alternatively, the amount of material absorbed on the grating can be determined sensitively from a precise measurement of the in-coupling wavelength (“spectral interrogation”). A tunable light source is required in order to perform such a measurement, rendering it complex and expensive. Waveguide grating sensors are not known to be photoluminescent (PL) and therefore do not provide emitted light wavelength shifts for the detection of absorbed molecules.
Double grating sensors, which work on the angle interrogation principle are also known, see e.g. I. Szendro, Proc. SPIE vol. 4284 (2001) pp. 80-86. Label-free biosensors using an optical waveguide with induced Bragg grating of variable strength have also been suggested recentlyn (A V. Dotsenko et al. Sensors and Actuators B, vol. 94 (2003) pp. 116-121, 2003).
The application of resonant micro-cavity structures (also referred to herein simply as micro-cavities or micro-resonators) to optical biosensing is also known. Specifically, a biosensor based on a photo-luminescent porous silicon microcavity was disclosed by Chan et al. in various publications (Phys. Stat. Sol. (a) vol. 182, (2000) p. 541; Proc. SPIE, vol. 3912 (2000) p. 23; Comput. Phys. vol. 12, (1998) p. 360; J. Am. Chem. Soc. Vol. 123, (2001) p. 11797; and U.S. patent application Ser. No. 20020192680. Chan's device is a “bulk” device, which includes a porous semiconductor structure comprising a central layer interposed between upper and lower layers, each of the upper and lower layers including strata of alternating porosity; and one or more probes coupled to the porous semiconductor structure, the one or more probes binding to a target molecule, whereby a detectable change occurs in a refractive index of the biological sensor upon binding of the one or more probes to the target molecule. This type of sensor is therefore based on spectral interrogation using self-emitted light. A major problem with such a structure is that the sensed material has to diffuse into the sensor bulk (volume). Consequently, the sensor responds slowly, and the target material molecule size is limited to be much smaller than the pore size (which is typically in the 10 to 20 nm range). In addition, the emission of light from porous silicon is notoriously inefficient.
In a recent U.S. patent application Ser. No. 20040223881, Cunningham et al disclose an apparatus and method for detection of peak wavelength values of calorimetric resonant optical biosensors using tunable filters and tunable lasers. Biomolecular interactions may be detected on a biosensor by directing collimated light towards a surface of the biosensor. Molecular binding on the surface of the biosensor is indicated by a shift in the peak wavelength value of reflected or transmitted light from the biosensor, while an increase in the wavelength corresponds to an increase in molecular absorption. A tunable laser light source may generate the collimated light and a tunable filter may receive the reflected or transmitted light and pass the light to a photodiode sensor. The photodiode sensor then quantifies an amount of the light reflected or transmitted through the tunable filter as a function of the tuning voltage of the tunable filter. A major disadvantage of this scheme of detection is that the tunable filter transmits a different wavelength in each direction. Therefore, if the medium between the filter and the spectrometer is diffusive (like a biological cell extract or tissue) the measurement cannot be done. In addition, this setup is complex and expensive.
Also known are disk resonator photonic biosensors, see for example R W Boyd and J. E. Heebner, Applied Optics, vol. 40 (2001) pp. 5742-5747. These biosensors are based on high-finesse, whispering-gallery-mode disk resonators and operate by means of monitoring the change in transfer characteristics of the disk resonator when biological materials fall onto its active area. High sensitivity is achieved because the light wave interacts many times with each pathogen as a consequence of the resonant recirculation of light within the disk structure. Specificity of the detected substance can be achieved when a layer of antibodies or other binding material is deposited onto the active area of the resonator.
Further, radial Bragg ring resonators (also referred to as annular Bragg resonators or ABRs) are also known, as disclosed for example in U.S. patent application Ser. No. 20040247008 by J. Scheuer and A. Yariv, as well as in related publications (e.g. J. Scheuer et al. Proc. SPIE. vol. 5333 (2004) pp. 183-194; WMJ. Green et al. Applied Physics Letters vol. 85, (October, 2004) pp. 3669-3671; J. Scheuer et al., Optics Letters, vol. 29 (November, 2004) pp. 2641-2643; J. Scheuer and A. Yariv, Physical Review E, vol. 70, (September, 2004) paper No. 036603 Part 2; and W M J Green et al, J. Vac. Sci. Technol. B, vol. 22, (November/December, 2004) pp. 3206-3210). Such structures comprise a closed loop resonator having a distributed Bragg reflector for confining the light within a guiding core. In one embodiment, the light is confined from both the internal and the external sides of the device forming a guiding channel (defect), or just by the external side forming a disk resonator. Although the perfectly circular shape is generally preferred, the resonator could be of any closed loop shape such as an ellipse, etc. The Bragg reflectors can be of any type of distributed reflector such as, for example, a photonic bandgap crystal where the Bragg reflector is constructed by a series of holes in a dielectric material. The resonator may be used to obtain a laser. One limitation of such resonators is the requirement for a closed loop. Also, as reported in Proc. SPIE. vol. 5333 (2004), resonators fabricated in a 250 nm InGaAsP membrane had to be transferred and mounted on a sapphire substrate for better optical confinement of their modes, all rather complicated and expensive processes. There is also no enabling description of the use of ABRs for sensing prior to the priority date of this application.
There is thus a recognized need for, and it would be advantageous to have, a biosensor that can be spectrally interrogated from afar, and which is sensitive, has high specificity, and is inexpensive and simple to manufacture and use.